Chronic Pain Management Research and the Opioid Crisis


     
Chronic Pain Management Research and the Opioid Crisis Developing novel drugs for chronic pain management — both more effective and less addictive than opioids — will reduce the number of patients at risk of opioid dependence.

Chronic Pain and the Opioid Crisis

More than 25% of Americans suffer from chronic pain. This is on par with adults from equivalent regions; between 10-25% of adults in other western countries experience chronic pain, while some estimates of chronic pain incidence among adults in the United Kingdom are as high as 50% of the population1.

While chronic pain incidence is similar in Europe, Canada, and the United States, opiates are more widely prescribed — and abused — in the US.

Opioids have been found to be relatively ineffective for treating chronic pain conditions, often leading to tolerance and hyperalgesia with long term use2,3.

Furthermore, long term use of opioids for chronic pain has directly contributed to the opioid crisis in the US: as new prescribing standards are instituted, patients seek black market pills and heroin to manage their pain.

This cycle of ineffective use, dependence, and drug abuse can best be addressed through developing more effective and less addictive treatments for chronic pain.

The Call for Novel Pain Management Therapeutics

Dr. Tom Price, Secretary of the US Department of Health and Human Services, stated that his agency will pursue five main strategies to combat the opioid epidemic:

  1. Increase access to addiction recovery treatment.
  2. Promote access to overdose-reversal drugs.
  3. Increase public health surveillance.
  4. Provide support for current research on addiction.
  5. Encourage better pain management practices4.
Researchers are responding to the need for more effective pain treatments by taking a deeper look at the mechanisms of pain, ways to reduce abuse potential, and factors which impact the efficacy of existing compounds.

Examples of this work include:

  • Development of compounds which activate different opiate receptors than traditional opioid drugs5.
  • Identification of new plant-derived compounds for management of chronic pain6,7,8,9.
  • Compounds which complement opiate efficacy, such as gabapentin, thus requiring smaller doses of opiates for similar efficacy10.
  • Adding abuse deterrents or making extended release formulas for existing drugs.
  • Development of new opioids with fewer adverse effects11.

Chronic Pain Management Research

To develop new therapeutics, researchers seek to better understand and model pain more effectively in preclinical experiments. It is just as critical to model the development of tolerance and potential for abuse, all of which require predictive animal models.

Animal Models of Chronic Pain

There are various methods to classify pain, such as by the level of intensity (mild to severe), by duration (acute to chronic), or by the cause of the pain (such as neuropathic or nociceptive).

Animal models of chronic pain are generally classified as inflammatory, neuropathic, visceral, or nociceptive (in mechanical and thermal models).

  • Examples of inflammation models used for studying pain include induced models of arthritis, utilizing either Complete Freund's Adjuvant or Type II collagen.
  • Visceral pain models typically involve injection of an irritant into the intraperitoneal cavity.
  • The most commonly used models of neuropathic pain are surgical models including partial sciatic nerve ligation, sciatic nerve ligation, and chronic constriction injury.
Access to animal models that effectively model human pain is essential to development of new therapeutics for management of chronic and acute pain. Pain model development must consider the type of pain to be modeled and the pain assessments which will be used. Further, new pain models must be validated for sensitivity and specificity before they can be used in drug discovery12,13.

Conclusion

Discovery of new therapeutics for managing chronic pain is of vital importance for reducing opiate abuse. Mouse and rat models play a key role in understanding pain signaling and pathways, as well as the mechanisms of dependence and addiction.

Rodent models are the most commonly used in pain studies as they are small, relatively inexpensive, and feature a variety of well-defined models for studying various aspects of pain and treatment.

References:
1. A. Morrone, et. al. "Opioids Resistance in Chronic Pain Management." Current Neuropharmacology (2017): 444-456.
2. Avery, T. Gov't agencies, orgs discuss opioid epidemic at national Rx conference, drugaddictionnow.com 29 April 2017. 6 May 2017.
3. Elhabazi K., et al. "Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities." J. Vis. Exp. (2014): e51264.
4. Fayaz A, et al. "Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies." BMJ (2016): 13.
5. Jayadeva V, et al. "Kratom (Mitragyna speciosa) Use in a Veteran With Chronic Pain." American Journal of Psychiatry Residents (2017): 13-15.
6. Manglik A, et al. "Structure-based discovery of opioid analgesics with reduced side effects." Nature (2016): 185-90.
7. Mogil JS, et al. "The necessity of animal models in pain research." Pain (2010): 12-17.
8. Papathanasiou T, et al. "Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain." European Journal of Pharmaceutical Sciences (2016): 97-105.
9. Prozialeck WC, et al. "Pharmacology of Kratom: An Emerging Botanical Agent With Stimulant, Analgesic and Opioid-Like Effects." The Journal of the American Osteopathic Association (2012): 792-99.
10. Schaller SJ, et al. "Pharmacokinetics cannot explain the increased effective dose requirement for morphine and midazolam in rats during their extended administration alone or in combination." J Pharm Pharmacol. (2017): 82-88.
11. Shoaib M, et al. "Scientific investigation of crude alkaloids from medicinal plants for the management of pain." BMC Complementary and Alternative Medicine (2016).
12. Singh D, et al. "Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature." Brain Research Bulletin (2016): 41-46.
13. Spahn V, et al. "Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development." Expert Opinion on Investigational Drugs (2017): 155-60.